Long Term Objective: to determine whether early interventional therapies can delay, prevent, or reverse the development of Type 1 diabetes. Specific Aims: intervention trials for subjects with pre-diabetes and new onset diabetes The Diabetes Prevention Trial - Type 1 (DPT-1): to determine whether the early intervention use of insulin in nondiabetic relatives of persons with Type 1 diabetes can delay their development of Type 1 diabetes as a clinical disease. Insulin is used for this purpose since it is a well characterized antigen specifically produced by beta cells. Research design: the parenteral antigen protocol enrolled subjects found to be at high risk (greater than 50 percent) for development of diabetes in the next 5 years. Subjects randomized to the insulin-treated group received insulin intravenously for 4 days each year and two injections of Ultralente each day (before breakfast and before bedtime). The oral antigen protocol enrolls subjects found to be at intermediate risk (25-50 percent) for the development of Type 1 diabetes in the next 5 years. This is a double-blind study and all subjects take 1 capsule daily, with half receiving the antigen and the others receiving a placebo. Levels of antibodies, insulin, C-peptide, HbA1C and glucose are followed. The main study endpoint is two ?diabetic? oral glucose tolerance tests (OGTT) performed on different days. Immunotherapy Trial in New Onset Type 1 Diabetes: to test the hypothesis that mycophenolate mofetil (MMF alone or with daclizumab (DZB) will prolong the period of C-peptide production in subjects with new onset Type 1 diabetes. A secondary aim is to provide the clinical material for the validation of surrogate markers for immunity to islet beta-cells. This study is innovative in that these agents have not been previously evaluated but are rational choices for intervention in an autoimmune disorder. Research design: Levels of autoantibodies and T cell reactivity to islet autoantigens, both of which are surrogate immunological parameters specific for Type 1 diabetes will be followed. Measures of immune modulation will include serologic and T cell reactivity to recall antigens. The metabolic end-points of this study will be fasting and stimulated C-peptide, hemoglobin A1C, and total insulin dose. If this study has a positive outcome, then we would propose a similar study in people at high risk for developing Type 1 diabetes.